Thioacetamide (TAA) has been used in development of animal models of acute hepatic encephalopathy (AHE). This experimental study was designed to evaluate effects of oral administration of vitamin C, vitamin E and their combination on liver and brain enzymes and their histologic and ultrastructure changes. Eighty Wistar rats were included and divided into five groups (16 each). Group 1 (control) received saline once intraperitoneally (IP) then administered orally saline and corn oil for 3 days. Group 2 [hepatotoxic (TAA)] were received TAA (300mg/kg) once intraperitoneally (IP). Group 3 (vitamin C and TAA) received TAA (300mg/kg) once intraperitoneally (IP) and then administered orally vitamin C (100mg/kg) daily for 3 days. Group 4 (vitamin E and TAA) received TAA (300mg/kg) once intraperitoneally (IP) and then administered orally vitamin E (200mg/kg) daily for 3 days. Group 5 (vitamin C and vitamin E and TAA) received TAA (300mg/kg) once intraperitoneally (IP) and then administered orally vitamin C (100mg/kg) in combination with vitamin E (200mg/kg) daily for 3 days. All rats were sacrificed 24h after last treatment under anesthesia. Blood samples were collected and serum was obtained for analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), total protein, triglyceride, cholesterol using spectrophotometer and ELISA kits. Liver and brain were extracted and tissue homogenate was used to measure malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO). Histological and ultrastructure examination were done. TAA induced significant increase of MDA and decreased in GSH and NO in both liver and brain homogenate with more liver affection, and increased in serum levels of AST, ALT, triglyceride, cholesterol and decreased in total protein. Furthermore, there is decrease in serum levels of AST, ALT, triglyceride, cholesterol and tissue levels of MDA and elevated serum total protein and tissue GSH and NO under the umbrella of vitamin C and vitamin E and their combination, although vitamin E is more efficient. These data showed protective effect of vitamins C and E, especially vitamin E against oxidative stress and hepatic and brain damage, and histological architecture of the liver in rats' model of acute hepatic encephalopathy elicited by TAA.